Redox Center Modification of Lapachones towards the Synthesis of Nitrogen Heterocycles as Selective Fluorescent Mitochondrial Imaging Probes

Santos, Fabíola S. dos; Dias, Gleiston G.; Freitas, Rossimiriam Pereira de; Santos, Lucas S.; Lima, Guilherme Ferreira de; Duarte, Hélio A.; Simone, C. A. De; Rezende, Lidia M. S. L.; Vianna, Monique Jacob Xavier; Corrêa, José R.; Neto, Brenno A. D.; Júnior, Eufrânio N. da Silva

doi:10.1002/ejoc.201700227

Cited by 22 publications

(12 citation statements)

References 63 publications

(46 reference statements)

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“…[ 86 ] 188–189 °C); δ H (400 MHz; CDCl 3 ) 8.10 (1 H, d, J 7.6, ArC H ), 7.68–7.64 (2 H, m, 2 x ArC H ), 7.63–7.57 (1 H, m, ArC H ), 2.97 (2 H, s, C H 2 ), 1.63 (6 H, s, 2 x C H 3 ); δ C (101 MHz; CDCl 3 ) 181.4 ( C = O), 175.7 ( C = O), 168.8 (Ar C ), 134.5 (Ar C H), 131.9 (Ar C H), 130.9 (Ar C ), 129.3 (Ar C H), 127.9 (Ar C ), 124.6 (Ar C H), 115.0 (Ar C ), 93.8 [ C (CH 3 ) 2 ], 39.3 ( C H 2 ), 28.4 (2 x C H 3 ). All data were in general agreement with the literature [ 83 , 86 ].…”

Section: Methodssupporting

confidence: 91%

“…[66] 226-229˚C); ν max (NaCl discs)/cm - . All data were in general agreement with the literature [82,83].…”

Section: Chemical Synthesissupporting

confidence: 91%

“…The crude product was purified by recrystallisation from n -hexane to give the dione 45 (73 mg, 52%) as an orange solid; mp 123–125 °C (from n -hexane), (lit. [ 83 ] 121–122 °C); ν max (NaCl discs)/cm -1 3364 (O-H), 2928 (C-H), 2910 (C-H), 1662 (C = O), 1645 (C = O), 1627 (C = C), 1593 (C = C); δ H (400 MHz; CDCl 3 ) 8.15 (1 H, d, J 7.6, ArC H ), 8.11 (1 H, d, J 7.6, ArC H ), 7.78 (1 H, td, J 7.6, 1.1, ArC H ), 7.71 (1 H, td, J 7.6, 1.1, ArC H ), 7.55 (1 H, br s, O H ), 6.02 (1 H, br s, C H ), 2.01 (3 H, s, C H 3 ), 1.70 (3 H, s, C H 3 ); δ C (101 MHz; CDCl 3 ) 184.8 ( C = O), 181.6 ( C = O), 151.2 ( C ), 143.6 ( C ), 134.9 (Ar C H), 133.0 (Ar C H), 132.9 ( C ), 129.5 ( C ), 126.9 (Ar C H), 126.1 (Ar C H), 120.9 ( C ), 113.7 ( C H), 26.6 ( C H 3 ), 21.8 ( C H 3 ); m/z (ESI + ) 251 (5%, M+Na + ), 229.0862 (100, M+H + C 14 H 13 O 3 requires 229.0859). All data were in general agreement with the literature [ 83 – 85 ].…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

et al. 2020

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During inflammation, dysregulated neutrophil behaviour can play a major role in a range of chronic inflammatory diseases, for many of which current treatments are generally ineffective. Recently, specific naturally occurring tanshinones have shown promising anti-inflammatory effects by targeting neutrophils in vivo, yet such tanshinones, and moreover, their isomeric isotanshinone counterparts, are still a largely underexplored class of compounds, both in terms of synthesis and biological effects. To explore the anti-inflammatory effects of isotanshinones, and the tanshinones more generally, a series of substituted tanshinone and isotanshinone analogues was synthesised, alongside other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of neutrophilic inflammation revealed differential anti-inflammatory profiles in vivo, with a number of compounds exhibiting promising effects. Several compounds reduce initial neutrophil recruitment and/or promote resolution of neutrophilic inflammation, of which two also result in increased apoptosis of human neutrophils. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting the recruitment of neutrophils to inflammatory sites, making this a particularly attractive candidate for potential pro-resolution therapeutics, as well as a possible lead for future development of functionalised tanshinones as molecular tools and/or chemical probes. The structurally related β-lapachones promote neutrophil recruitment but do not affect resolution. We also observed notable differences in toxicity profiles between compound classes. Overall, we provide new insights into the in vivo anti-inflammatory activities of several novel tanshinones, isotanshinones, and structurally related compounds.

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Section: Methodssupporting

confidence: 91%

“…[66] 226-229˚C); ν max (NaCl discs)/cm - . All data were in general agreement with the literature [82,83].…”

Section: Chemical Synthesissupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

et al. 2020

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“…Based on our interest in the development of new bioimaging agents [38–40], we disclose herein the design, synthesis, properties and application of a new fluorogenic BTD derivative as a water-soluble selective plasma membrane probe for bioimaging experiments.…”

Section: Introductionmentioning

confidence: 99%

Plasma membrane imaging with a fluorescent benzothiadiazole derivative

Carvalho¹,

Corrêa²,

Paiva³

et al. 2019

Beilstein J. Org. Chem.

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This work describes a novel fluorescent 2,1,3-benzothiadiazole derivative designed to act as a water-soluble and selective bioprobe for plasma membrane imaging. The new compound was efficiently synthesized in a two-step procedure with good yields. The photophysical properties were evaluated and the dye proved to have an excellent photostability in several solvents. DFT calculations were found in agreement with the experimental data and helped to understand the stabilizing intramolecular charge-transfer process from the first excited state. The new fluorescent derivative could be applied as selective bioprobe in several cell lines and displayed plasma-membrane affinity during the imaging experiments for all tested models.

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“…Since the design of innovative and often unconventional synthetic approaches is often necessary to assemble new fluorescent scaffolds (De Moliner et al, 2017 ), we envisioned a strategy exploiting the potential of natural products as advanced intermediates toward the generation of phenazine probes for LDs (Scheme 1 ) (Carvalho et al, 2004 ; Emery et al, 2010 ; Dias et al, 2016 ; Gontijo et al, 2016 ; de Souza et al, 2017 ). As a part of our ongoing interest in medicinal chemistry (Yraola et al, 2004 ; Vendrell et al, 2007 , 2009 ) and the synthesis and application of novel fluorescent probes for imaging of subcellular organelles (Jardim et al, 2015 ; dos Santos et al, 2017 ) phenazines P1 and P3-P7 were prepared from the naturally-occurring lapachol. Herein we report the chemical synthesis and photophysical characterization of this new set of compounds as well as cell imaging experiments that demonstrate their suitability for the fluorescence staining of LDs in live cells.…”

Section: Introductionmentioning

confidence: 99%

Quinone-Derived π-Extended Phenazines as New Fluorogenic Probes for Live-Cell Imaging of Lipid Droplets

et al. 2018

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We describe a new synthetic methodology for the preparation of fluorescent π-extended phenazines from the naturally-occurring naphthoquinone lapachol. These novel structures represent the first fluorogenic probes based on the phenazine scaffold for imaging of lipid droplets in live cells. Systematic characterization and analysis of the compounds in vitro and in cells led to the identification of key structural features responsible for the fluorescent behavior of quinone-derived π-extended phenazines. Furthermore, live-cell imaging experiments identified one compound (P1) as a marker for intracellular lipid droplets with minimal background and enhanced performance over the lipophilic tracker Nile Red.

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Redox Center Modification of Lapachones towards the Synthesis of Nitrogen Heterocycles as Selective Fluorescent Mitochondrial Imaging Probes

Cited by 22 publications

References 63 publications

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

Plasma membrane imaging with a fluorescent benzothiadiazole derivative

Quinone-Derived π-Extended Phenazines as New Fluorogenic Probes for Live-Cell Imaging of Lipid Droplets

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